Oral herpes, an infection caused by the herpes simplex virus, is estimated to be present in 50 to 80 percent of the American adult population. Nearly 20 percent, over 50 million people, are infected with genital herpes, also caused by the herpes simplex virus, and the majority of these cases may be unaware they even have it. Studies show that more than 500,000 Americans are diagnosed with genital herpes each year, and the largest increase is occurring in young teens.
Cold sores, sometimes called fever blisters, are clusters of small blisters on the lip and outer edge of the mouth. The skin around the blisters is often red and inflamed. The blisters can break open, weep a clear fluid, and then scab over after a few days. Complete healing may take 7 to 10 days. Cold sores are caused by the herpes simplex virus (HSV). There are two types of herpes simplex virus (HSV). HSV-1 usually leads to lip and mouth sores (herpes labialis), while HSV-2 most often leads to genital herpes. However, both virus types can cause cold sores or genital herpes if skin comes into contact with either type. Cold sores are caused by the herpes simplex virus (HSV). There are two types of herpes simplex virus (HSV). HSV-1 usually leads to lip and mouth sores (herpes labialis), while HSV-2 most often leads to genital herpes. However, both virus types can cause cold sores or genital herpes if skin comes into contact with either type. Cold sores are estimated to be present in 50 to 80 percent of the American adult population. Nearly 20 percent, over 50 million people, are infected with genital herpes, also caused by the herpes simplex virus, and the majority of these cases may be unaware they even have it. Studies show that more than 500,000 Americans are diagnosed with genital herpes each year, and the largest increase is occurring in young teens.
There is no cure for cold sores and genital herpes to date. Efforts to develop a herpes vaccine by biotechnology companies are ongoing. Until an effective herpes vaccine or cure for HSV infection is found, the prevailing approach to treatment continues to be suppressive antiviral therapy.
Topical creams are commonly used to treat cold sores. Many are prescription medications that can slightly shorten the duration of cold sores, usually by just 1 to 2 days. Studies are ongoing to determine the effectiveness of these creams (Boon 2000). Some experts find that even when nonprescription topical creams are used frequently, every 2 hours during wake time, at the first sign of an outbreak, they may only speed recovery time by a few hours or a day (Habif 2004).
Penciclovir cream (such as Denavir) is an antiviral cream that may reduce healing time by 1 to 2 days, especially if the cold sore was triggered by sunlight exposure (Sacks 2001; Herpes 2003). It also reduces pain, itching, burning, and tenderness associated with cold sores. Penciclovir cream may cause side effects such as mild pain or stinging when it is applied. It is possible, although rare, that the cream may also cause a skin rash or headache.
Acyclovir ointment and cream are used up to six times a day for 10 days. Treatment with acyclovir ointment works best if it is used at the first sign of cold sore symptoms. The cream can improve healing time by up to ½ a day. Side effects of acyclovir ointment may include mild pain or stinging at the site of application. The cream may cause temporary skin irritation.
Tetracaine cream is a nonprescription topical anesthetic that lessens the physical sensation and can relieve pain and itching associated with cold sores. Initial studies show that tetracaine cream can reduce the healing time of cold sores by up to 2 days (Habif 2001). Tetracaine cream is applied to cold sores up to six times daily for best results. Pain and itching are relieved usually within 2 to 3 days after first applying tetracaine cream.
Docosanol 10% (Abreva) is a newer nonprescription cream that is safe and effective for treating cold sores. It is most effective when applied at the first signs of a cold sore outbreak (Sacks 2001). It is the first nonprescription cold sore medication approved by the U.S. Food and Drug Administration (FDA) to shorten healing time and duration of symptoms.
Valacyclovir was recently approved by the U.S. Food and Drug Administration (FDA) as a one-day treatment to reduce cold sore duration in people 12 years and older (Habif 2004). It is absorbed by the body much better than some other antiviral medications (such as acyclovir). Possible side effects include skin rash, allergic reaction, headache, dizziness, insomnia, depression, and fatigue.
Native to India, the sandalwood tree is used for many purposes; the wood for decorative carvings, the oil for fragrance in incense, perfumes, and soaps. Both its wood and oil have also been employed medicinally for a wide variety of conditions. In traditional Indian (Ayurvedic) medicine, sandalwood was used to treat gonorrhea and to decrease sex drive. Traditional Chinese medicine also lists sandalwood as a treatment for gonorrhea, as well as for stomachache and vomiting. In Europe, sandalwood was used to treat fever and pain. However, no clinical evidence exists to support any of these applications.
The main constituent of sandalwood oil is santalol. This primary sesquiterpene alcohol forms more than 90 percent of the oil and is present as a mixture of two isomers, α-santalol and β-santalol, the former predominating. The characteristic odor and medicinal properties of sandalwood oil are mainly due to the santalols. The other constituents reported in sandalwood oil include: the hydrocarbons santene, nor-tricycloekasantalene and α- and β-santalenes; the alcohols santenol and teresantalol; the aldehydes nor-tricycloekasantalal, and isovaleraldehyde; the ketones 1-santenone and santalone; and the acids teresantalic acid occurring partly free and partly in esterfied form, and α- and β-santalic acids. Table I sets forth the certain constituents of a fresh sandalwood oil.
TABLE IComparative composition of Sample of Sandalwood OilCompoundWeight Percentage Compositionα-santalene0.82epi-β-santalene0.97β-santalene1.40α-santalal2.90cis-α-santalyl acetate—β-santalal0.56cis-β-santalyl acetate—cis-α-santalol50.0 (Z)-trans-α-begamotol3.90epi-β-santalol4.10cis-β-santalol20.9 trans-β-santalol1.50cis-lanceol1.70cis-nuciferol1.10spirosantalol1.20
The total alcohol content varies from 80% to 93% by weight. The santalol content also varies from species to species of Santalum. Table II sets forth the santalol content of various Santalum species.
TABLE IISantalol content of various Santalum speciesPercentage compositionSantalum SpeciesOriginα-santalolβ-santalolS. album (1)*China50.018.1S. album (4)India46.6-59.924.6-29.0 S. album (5)Indonesia 7.1-48.68.7-25.2S. yasi (1)Fiji54.032.8S. papuanum (1)Papua, New Guinea26.315.5S. spicatum (3)Australia27.9-35.34.0-29.2*No. of samples
Germany's Commission E has approved sandalwood oil for the treatment of bladder infections, not to be used alone, but along with other therapies (Blumenthal 1998). Sandalwood oil is said to act as an antiseptic in the urinary system; if this is correct, it might help to rid the body of the bacteria that cause these infections (Leung 1996), but there is no reliable evidence as yet to verify this belief.
In test tube studies, sandalwood oil was found to slow the growth of herpes virus (Benencia 1999). An animal study found that components isolated from sandalwood caused responses similar to those seen with medications used to treat schizophrenia (Okugawa 1995). However, this evidence is far too weak to indicate that sandalwood is a useful treatment for either of these conditions. Sandalwood oil is also advertised for other therapeutic uses, including bronchitis, sore throat, and persistent cough. External application of a sandalwood paste is sometimes suggested for acne, skin rashes, or dry skin. None of these proposed uses, however, have been scientifically studied.
The safety of sandalwood oil has not been formally evaluated. Reported side effects include nausea and itching (Blumenthal 1998). Sandalwood paste applied externally has been reported to cause skin irritation on rare occasions. There is also one case report of a man developing a skin rash after burning large quantities of sandalwood incense (Sandra 1996; Sharma 1987; Hayakawa 1987).
The sandalwood oil displayed chemoprotective effects on 7,12-dimethylbenz(a)anthracene-(DMBA)-initiated and 12-O-tetradecanoyl phorbol-13-acetate(TPA)-promoted skin papillomas, and TPA-induced ornithine decarboxylase (ODC) activity in mice. Treatment with sandalwood oil or santalol significantly decreased papilloma incidence by 67%, multiplicity by 96%, and TPA-induced ODC activity by 70% (Dwivedi and Abu-Ghazaleh 1997; Dwivedi 2003). Kaur et al (2005) identify the apoptotic effect of -santalol, and define the mechanism of apoptotic cascade activated by this agent in A431 cells, which might be contributing to its overall cancer preventive efficacy in mouse skin cancer models. The sandalwood oil was found to enhance glutathione S-transferase (GST) activity and acid soluble sulphydryl (SH) levels in the liver of adult male Swiss albino mice, suggesting a possible chemopreventive action. (Banerjee et al. 1993).
U.S. Pat. No. 6,132,756 discloses the use of sandalwood oil for the treatment of warts caused by the human papillomavirus (HPV) in humans. U.S. Pat. No. 6,406,706 discloses the use of α- and β-santalols, or mixtures or derivatives thereof, to prepare medicaments for the treatment of viral-induced tumors i.e., warts caused by the human papillomavirus (HPV) in humans. U.S. Pat. No. 5,225,608 discloses substituted cyclohexanol compounds that are similar to beta-santalol and that possessing a sandalwood aroma, but lacks the carbon chains claimed by the present invention. U.S. Pat. No. 3,970,706 discloses a method of making alpha-santalol, but not a method of making an ester of santalol or using a santalol compound.
The chemical formula for α- and β-santalol is C15H24O and the chemical structures are shown in FIG. 1. The chemical names for santalol (α- and β) are 2-methyl-5-(2,3-dimethyltricyclo[2.2.1.0(2.6)]hept-3-yl)pent-2-enol and 2-methyl-5-(2-methyl-3-methylenebicyclo[2.2.1]hept-2-yl)pent-2-enol, respectively.
Santalols may be obtained by fractional distillation of sandalwood oil, with the α- and β-isomers appearing in different ratios and with the α-isomer being more abundant. Santalol can be isolated from sandalwood oil by distillation under vacuum, BP 95° C./0.5 mm Hg. The santalols are colorless to pale yellow in appearance.
Santalols are commonly used in the flavor and fragrance industries and are considered woody, cedar-like, warm and herbaceous. They may be used in perfumes, baked goods, frozen dairy, soft candy, gelatin pudding, chewing gum and non-alcoholic beverages. As such, they are non-toxic and harmless when used either for external application on the skin or internal consumption for flavor.
Since sandalwood oil contains 80-90% of alcohol, excess application to the skin can cause irritation and itching. To eliminate the irritation and itching, the alcohols can be esterified as they are milder to the skin.
The purpose of the present application is to disclose the unexpected discovery that the esterified sandalwood oil and esterified santalols are extremely effective in treating cold sores and genital herpes in humans.